Article
Oncology
Miguel A. Villalona-Calero, John P. Diaz, Wenrui Duan, Zuanel Diaz, Eric D. Schroeder, Santiago Aparo, Troy Gatcliffe, Federico Albrecht, Siddhartha Venkatappa, Victor Guardiola, Sara Garrido, Muni Rubens, Fernando DeZarraga, Hao Vuong
Summary: This study demonstrates the significant antitumor activity of pembrolizumab in malignancies without current FDA approved indications and with functional Fanconi anemia deficiency. The results support further evaluation of FATSI as a discriminatory biomarker for population-selected studies.
BIOMARKER RESEARCH
(2022)
Editorial Material
Cell Biology
Jasmine D. Peake, Kalisse I. Horne, Chiaki Noguchi, John P. Gilligan, Eishi Noguchi
Summary: Alcohol can cause cellular accumulation of acetaldehyde, a major carcinogen, and individuals with deficiency in acetaldehyde detoxification or the Fanconi anemia DNA repair pathway have an increased risk of esophageal squamous-cell carcinoma. This study reveals that acetaldehyde induces DNA damage at the replication fork, leading to replication stress and activation of cell cycle checkpoints. It also demonstrates that the p53 DNA damage response is elevated in response to acetaldehyde and the FA pathway limits genomic instability. These findings highlight the importance of the FA pathway and p53 DNA damage response in protecting against genomic instability and esophageal carcinogenesis.
Review
Genetics & Heredity
Masamichi Ishiai
Summary: The Fanconi anemia (FA) DNA repair pathway is activated through monoubiquitination of FANCD2 and its binding partner FANCI, regulated by the ATR kinase. This process serves as a good example of ATR's contribution to genome stability.
Review
Cell Biology
Yeldar Baiken, Damira Kanayeva, Sabira Taipakova, Regina Groisman, Alexander A. Ishchenko, Dinara Begimbetova, Bakhyt Matkarimov, Murat Saparbaev
Summary: Complex DNA damage (CDD) is challenging to repair due to its complex structure compared to singular lesions, and if left unrepaired, can lead to serious consequences such as chromosomal rearrangements and genome instability. Repair of CDD requires the concurrent involvement of multiple DNA repair pathways to ensure effective repair.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jacob Edogbanya, Daniela Tejada-Martinez, Nigel J. Jones, Amit Jaiswal, Sarah Bell, Rui Cordeiro, Sipko van Dam, Daniel J. Rigden, Joao Pedro de Magalhaes
Summary: C1ORF112 gene, initially identified for its co-expression with cancer-associated genes and involvement in DNA repair and cell cycle regulation, remains poorly understood in terms of its molecular functions. Conservation across eukaryotes, with high conservation in primates, indicates a potentially essential role in mammalian development. Expression data reveals high levels in testes and overexpression in cancers, with potential links to DNA damage repair pathways such as Fanconi anaemia and homologous recombination.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Reproductive Biology
Jingyu Zhao, Yixin Zhang, Wenbo Li, Mengmeng Yao, Chuqi Liu, Zihan Zhang, Caiqin Wang, Xiaomei Wang, Kai Meng
Summary: The Fanconi anemia pathway plays a key role in repairing DNA interstrand crosslinking damage, and it is closely related to premature ovarian insufficiency.
BIOLOGY OF REPRODUCTION
(2023)
Article
Genetics & Heredity
Stanley Dean Rider Jr, French J. J. Damewood, Rujuta Yashodhan Gadgil, David C. C. Hitch, Venicia Alhawach, Resha Shrestha, Matilyn Shanahan, Nathen Zavada, Michael Leffak
Summary: Unbiased genetic screens using a lentiviral shRNA library identified genes that suppress break-induced mutagenesis in human cells with fragile non-B DNA. These genes have roles in DNA replication and repair, chromatin modification, responses to ionizing radiation, and replication fork-associated proteins. Novel loci implicated in BIR were also identified. Knockdown of selected candidates increased the frequency of nucleoside analog resistance and DNA rearrangements near the non-B DNA.
Article
Chemistry, Multidisciplinary
Xue Dong, Pei Pan, Qiu-Ling Zhang, Jing-Jie Ye, Peng Bao, Xuan Zeng, Xian-Zheng Zhang
Summary: This study developed a magnetic nanoparticle-mediated CRISPR/Cas9 system to target and inactivate the Mlh1 gene, resulting in enhanced tumor immunogenicity. In vitro and in vivo experiments demonstrated that this strategy effectively suppressed tumor growth and improved infiltration of CD8(+) T cells and response to immune checkpoint blockade therapy.
Article
Multidisciplinary Sciences
Jessica W. Luzwick, Eszter Dombi, Rebecca A. Boisvert, Sunetra Roy, Soyoung Park, Selvi Kunnimalaiyaan, Steffi Goffart, Detlev Schindler, Katharina Schlacher
Summary: The Fanconi anemia suppressor genes in mitochondria protect mtDNA replication forks, while degradation by MRE11 nuclease leads to loss of nascent mtDNA. Unlike nuclear DNA replication fork stability, mitochondrial replication fork protection does not require pathway activation, revealing a separation between the two stability pathways.
Review
Oncology
Panagiota Gianni, Evangelia Matenoglou, Georgios Geropoulos, Nirav Agrawal, Harsha Adnani, Stefanos Zafeiropoulos, Santiago J. Miyara, Sara Guevara, James M. Mumford, Ernesto P. Molmenti, Dimitrios Giannis
Summary: The development of breast cancer depends on various risk factors, including environmental, lifestyle, and genetic factors. Understanding the function and epidemiology of breast cancer susceptibility genes is crucial for the development of personalized therapies targeting unique tumor profiles. The Fanconi Anemia pathway plays a critical role in DNA damage response and repair, and specific mutations in this pathway have been identified in the majority of Fanconi Anemia patients.
CLINICAL BREAST CANCER
(2022)
Review
Biochemistry & Molecular Biology
Winnie Tan, Andrew J. Deans
Summary: The Fanconi Anemia (FA) pathway maintains genome stability by preventing DNA damage, with the FA core complex playing a central role in monoubiquitination of FANCI-FANCD2. Any mutations in the FA core complex can lead to defective monoubiquitination, resulting in various phenotypes including DNA damage sensitivity, birth defects, early-onset bone marrow failure, and cancer.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Article
Immunology
Shenghan Lou, Yufei Wang, Jian Zhang, Xin Yin, Yao Zhang, Yimin Wang, Yingwei Xue
Summary: The role of DNA damage repair (DDR) in gastric cancer remains to be fully understood. This study utilized gene set enrichment analysis to investigate the impact of DDR pathway profiling on clinical outcomes, biological functions, genetic variants, immune heterogeneity, and treatment responses. The results demonstrate distinct differences in DDR pathway activity between tumor and normal tissues, with correlations to patient survival, tumor phenotypes, and genome stability.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Masanori Oshi, Tae Hee Kim, Yoshihisa Tokumaru, Li Yan, Ryusei Matsuyama, Itaru Endo, Leonid Cherkassky, Kazuaki Takabe
Summary: In this study, the relationship between enhancement of DNA repair and cancer aggressiveness, tumor immune microenvironment, and patient survival in hepatocellular carcinoma (HCC) patients was investigated using a DNA repair pathway score. Results showed that the DNA repair pathway was enhanced in a stepwise manner during HCC carcinogenesis, particularly noted in grade 3 tumors. High DNA repair activity in HCC was associated with worse survival, increased intratumor heterogeneity, and mutation load.
Article
Oncology
Anna Huguet Ninou, Jemina Lehto, Dimitrios Chioureas, Hannah Stigsdotter, Korbinian Schelzig, Emma Akerlund, Greta Gudoityte, Ulrika Joneborg, Joseph Carlson, Jos Jonkers, Brinton Seashore-Ludlow, Nina Marie Susanne Gustafsson
Summary: DNA-damaging chemotherapeutics, such as platinum drugs, rely on the DNA repair capacity of cancer cells for efficacy, but cancer cells often develop resistance by altering their DNA damage response pathways. Targeting PFKFB3, which is commonly overexpressed in cancer, sensitizes cancer cells to platinum drugs and improves treatment efficacy by modulating the Fanconi anemia DNA repair pathway. Inhibition of PFKFB3 disrupts the assembly of key FA repair factors, prevents fork restart, and ultimately leads to an accumulation of DNA damage in replicating cells and fork collapse, enhancing the effectiveness of ICL-inducing cancer treatments.
Article
Environmental Sciences
Yun Zhao, Linqing Wei, Abderrahmane Tagmount, Alex Loguinov, Amin Sobh, Alan Hubbard, Cliona M. McHale, Christopher J. Chang, Chris D. Vulpe, Luoping Zhang
Summary: This study identified genes affecting formaldehyde toxicity in human hematopoietic cells using CRISPR screening, including those that increase sensitivity and resistance, along with related pathways and mechanisms. Results indicated a significant role for formaldehyde metabolism and the Fanconi anemia pathway in toxicity tolerance, and new network analyses revealed potential roles for one-carbon metabolism, fatty acid synthesis, and mTOR signaling in modulating formaldehyde toxicity.
Article
Hematology
Michele Cavo, Jesus San-Miguel, Saad Z. Usmani, Katja Weisel, Meletios A. Dimopoulos, Herve Avet-Loiseau, Bruno Paiva, Nizar J. Bahlis, Torben Plesner, Vania Hungria, Philippe Moreau, Maria-Victoria Mateos, Aurore Perrot, Shinsuke Iida, Thierry Facon, Shaji Kumar, Niels W. C. J. van de Donk, Pieter Sonneveld, Andrew Spencer, Maria Krevvata, Christoph Heuck, Jianping Wang, Jon Ukropec, Rachel Kobos, Steven Sun, Mia Qi, Nikhil Munshi
Summary: In this study, we explored the impact of minimal residual disease (MRD) on relapsed/refractory multiple myeloma (RRMM) and transplant-ineligible newly diagnosed multiple myeloma (TIE NDMM). The results showed that achieving complete response or better (>= CR) and MRD negativity were associated with improved progression-free survival (PFS) in both RRMM and TIE NDMM patients, regardless of the type of therapy or disease setting.
Letter
Hematology
Thomas Gastinne, Amandine Le Bourgeois, Marianne Coste-Burel, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Berthe-Marie Imbert, Thomas Drumel, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Anne Lok, Cyrille Touzeau, Benoit Tessoulin, Maxime Jullien, Sophie Vanthygem, Marie C. Bene, Philippe Moreau, Steven Le Gouill, Patrice Chevallier
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Paul G. Richardson, Fredrik Schjesvold, Katja Weisel, Philippe Moreau, Larry D. Anderson, Darrell White, Paula Rodriguez-Otero, Pieter Sonneveld, Monika Engelhardt, Matthew Jenner, Alessandro Corso, Jan Duerig, Michel Pavic, Morten Salomo, Meral Beksac, Albert Oriol, Jindriska Lindsay, Anna Marina Liberati, Monica Galli, Pawel Robak, Alessandra Larocca, Munci Yagci, Filiz Vural, Abraham S. Kanate, Ruiyun Jiang, Lara Grote, Teresa Peluso, Meletios Dimopoulos
Summary: This study showed that PVd significantly prolonged PFS in lenalidomide-pretreated patients with multiple myeloma at first relapse, across different age groups, renal function status, and cytogenetic abnormalities. PVd also improved overall response rate in all subgroups, with a safety profile consistent with previous reports.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Evangelos Terpos, Meletios A. Dimopoulos, Mario Boccadoro, Sosana Delimpasi, Meral Beksac, Eirini Katodritou, Philippe Moreau, Alessandra Pompa, Argiris Symeonidis, Jelena Bila, Albert Oriol, Maria-Victoria Mateos, Hermann Einsele, Ioannis Orfanidis, Katharine S. Gries, John Fastenau, Kevin Liu, Jianming He, Tobias Kampfenkel, Yanping Qiu, Himal Amin, Robin Carson, Pieter Sonneveld
Summary: In the APOLLO trial, daratumumab in combination with pomalidomide and dexamethasone showed significant clinical improvements in patients with relapsed/refractory multiple myeloma. Patient-reported outcomes (PROs) revealed that the addition of daratumumab to the treatment regimen did not negatively impact the health-related quality of life and even showed improvements in pain and fatigue.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Letter
Hematology
Sosana Delimpasi, Maria Victoria Mateos, Holger W. Auner, Maria Gavriatopoulou, Meletios A. Dimopoulos, Hang Quach, Halyna Pylypenko, Roman Hajek, Xavier Leleu, Tuphan Kanti Dolai, Dinesh Kumar Sinha, Christopher P. Venner, Reuben Benjamin, Mamta Krishnan Garg, Vadim Doronin, Yair Levy, Philippe Moreau, Yi Chai, Melina Arazy, Jatin Shah, Sharon Shacham, Michael G. Kauffman, Paul G. Richardson, Sebastian Grosicki
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Oncology
Maria-Victoria Mateos, Katja Weisel, Valerio De Stefano, Hartmut Goldschmidt, Michel Delforge, Mohamad Mohty, Michele Cavo, Ravi Vij, Joanne Lindsey-Hill, Dominik Dytfeld, Emanuele Angelucci, Aurore Perrot, Reuben Benjamin, Niels W. C. J. van de Donk, Enrique M. Ocio, Christof Scheid, Francesca Gay, Wilfried Roeloffzen, Paula Rodriguez-Otero, Annemiek Broijl, Anna Potamianou, Caline Sakabedoyan, Maria Semerjian, Sofia Keim, Vadim Strulev, Jordan M. Schecter, Martin Vogel, Robert Wapenaar, Tonia Nesheiwat, Jesus San-Miguel, Pieter Sonneveld, Hermann Einsele, Philippe Moreau
Summary: This is the first prospective study for relapsed/refractory multiple myeloma patients, showing a lack of clear standard of care in real-world practice for heavily pretreated patients and resulting in poor outcomes. This supports the need for new treatments with novel mechanisms of action.
Review
Oncology
Joan Blade, Meral Beksac, Jo Caers, Artur Jurczyszyn, Marie Von Lilienfeld-Toal, Philippe Moreau, Leo Rasche, Laura Rosinol, Saad Z. Usmani, Elena Zamagni, Paul Richardson
Summary: Extramedullary involvement is an aggressive form of multiple myeloma, with varied typical sites and incidence rates. Patients with EMD have poor prognosis and lower treatment efficacy. The lack of prospective studies limits strong recommendations for treatment approaches.
BLOOD CANCER JOURNAL
(2022)
Article
Hematology
Blandine Pouleau, Carole Estoppey, Perrine Suere, Emilie Nallet, Amelie Laurendon, Thierry Monney, Daniela Pais Ferreira, Adam Drake, Laura Carretero-Iglesia, Julie Macoin, Jeremy Berret, Maria Pihlgren, Marie-Agnes Doucey, Girish S. Gudi, Vinu Menon, Venkatesha Udupa, Abhishek Maiti, Gautam Borthakur, Ankita Srivastava, Stanislas Blein, M. Lamine Mbow, Thomas Matthes, Zeynep Kaya, Claire M. Edwards, James R. Edwards, Emmanuelle Menoret, Charlotte Kervoelen, Catherine Pellat-Deceunynck, Philippe Moreau, Eugene Zhukovsky, Mario Perro, Myriam Chimen
Summary: ISB 1342, a bispecific antibody targeting CD38 on tumor cells and CD3 epsilon on T cells, shows promising efficacy in killing daratumumab-resistant multiple myeloma cells. It has demonstrated high cytotoxicity and complete tumor control in preclinical studies, making it a potential option for patients refractory to previous anti-CD38 monoclonal antibody therapies.
Letter
Medicine, Research & Experimental
Kohar Kevork, Melanie Gouin, Valentin Letailleur, Patrice Chevallier, Cyrille Touzeau, Thomas Gastinne, Benedicte Piron, Benoit Tessoulin
CURRENT RESEARCH IN TRANSLATIONAL MEDICINE
(2023)
Article
Hematology
Salome Decombis, Celine Bellanger, Yannick Le Bris, Candice Madiot, Jane Jardine, Juliana Carvalho Santos, Delphine Boulet, Christelle Dousset, Audrey Menard, Charlotte Kervoelen, Elise Douillard, Philippe Moreau, Stephane Minvielle, Agnes Moreau-Aubry, Benoit Tessoulin, Gael Roue, Nicolas Bidere, Steven Le Gouill, Catherine Pellat-Deceunynck, David Chiron
Summary: This study identified the resistance mechanisms to targeted therapies in B-cell lymphomas and proposed a novel strategy to overcome this resistance. The study also discovered a resistance signature that could predict the response to conventional chemotherapy.
Article
Hematology
Benedicte Piron, Domitille Costes-Tertrais, Thomas Gastinne, Aude Marie Fourmont, Viviane Dubruille, Nicolas Blin, Philippe Moreau, Cyrille Touzeau, Benoit Tessoulin
Summary: This retrospective single-centre study investigated the outcomes of relapsed multiple myeloma patients who failed various treatments, and found that patients who failed anti-BCMA therapy had poor prognosis, highlighting the unmet medical need in this population.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Mathematical & Computational Biology
Alban Gaignard, Thomas Rosnet, Frederic De Lamotte, Vincent Lefort, Marie-Dominique Devignes
Summary: The rise of Open Science and Reproducibility in the Life Sciences necessitates the use of rich, machine-actionable metadata to facilitate the sharing and reuse of biological digital resources. To assess the FAIRness of metadata in digital resources, we propose FAIR-Checker, a web-based tool that offers comprehensive evaluations, recommendations, and metadata improvement assistance. Using Semantic Web standards and technologies, FAIR-Checker automatically assesses FAIR metrics and notifies users of missing or recommended metadata. We evaluate FAIR-Checker in the context of improving individual resource FAIRness and analyzing bioinformatics software descriptions.
JOURNAL OF BIOMEDICAL SEMANTICS
(2023)
Review
Biochemistry & Molecular Biology
Marine Djaffardjy, George Marchment, Clemence Sebe, Raphael Blanchet, Khalid Bellajhame, Alban Gaignard, Frederic Lemoine, Sarah Cohen-Boulakia
Summary: Data analysis pipelines are established as an effective means for bioinformatics data analysis and experiments. However, scripting languages are not sufficient for building large-scale pipelines capable of handling big data and running on high performance computing clusters. Scientific workflow systems provide modular, reproducible, and reusable solutions for bioinformatics data analysis pipelines.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Hematology
Maxime Jullien, Amandine Le Bourgeois, Marianne Coste-Burel, Pierre Peterlin, Alice Garnier, Marie Rimbert, Berthe-Marie Imbert, Steven Le Gouill, Philippe Moreau, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Anne Lok, Cyrille Touzeau, Thomas Gastinne, Benoit Tessoulin, Sophie Vantyghem, Marie C. Bene, Thierry Guillaume, Patrice Chevallier
Summary: Little is known about the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study found that B cell aplasia is the only factor predicting the absence of a specific immune response, and suggests administering the vaccine as soon as peripheral B cell levels can be detected.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Review
Hematology
Meletios A. Dimopoulos, Joseph Mikhael, Evangelos Terpos, Xavier Leleu, Philippe Moreau, Joan Blade, Jin Seok Kim, Keith Stockerl-Goldstein, Paul G. Richardson
Summary: This article reviews existing data on renal impairment (RI) and relapsed/refractory multiple myeloma (RRMM) to provide insights into available treatment options for this important population. Despite advances in treatment, RI continues to impact overall survival. Future trials should consistently include patients with RI and report their outcomes.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2022)